Increased cell proliferation and contractility of prostate in insulin resistant rats: Linking hyperinsulinemia with benign prostate hyperplasia

Abstract

The present investigation reports that HFD-feeding induced hyperinsulinemic condition leads to increased cellular proliferation, enhanced alpha-adrenoceptor mediated contraction, and enlargement of the prostate in rats.

Lipids in the Pathogenesis of Benign Prostatic Hyperplasia: Emerging Connections

“…Prostatic atrophy and increased apoptosis in the hypoinsulinemic rats (induced by selective -cell toxins, either streptozotocin or alloxan) further supports the view that insulin plays a central role in the prostatic growth and development (Arcolino et al, 2010;Ikeda et al, 2000;Suthagar et al, 2009;Vikram et al, 2008;Yono et al, 2008;Yono et al, 2005). Increased cell proliferation and enlargement of ventral prostate in rats kept on the diet rich in saturated fat was observed (Vikram et al, 2010b;Vikram et al, 2010c). Interestingly, pioglitazone (a synthetic PPAR receptor agonist) treatment led to decreased cell proliferation, increased apoptosis and restoration of prostatic weight in the diet-induced insulin-resistant rats (Vikram et al, 2010b;Vikram et al, 2010c).…”

“…Existing clinical/epidemiological and preclinical studies provide convincing evidence for the association between insulinresistance, metabolic disorder and type 2 diabetes with the BPH (Francisco and Francois, 2010;Vikram et al, 2010a;Wang and Olumi, 2011). Previous experimental studies in our laboratory suggested that insulin-resistance associated secondary rise in the plasma insulin level plays a central role in the prostatic enlargement Vikram et al, 2010a;Vikram et al, 2010c;. Other peptides such as insulinlike growth factor-I (IGF-I), IGF-I binding proteins (IGFBPs), growth hormone (GH), transforming growth factor-(TGF-β) family proteins are reported to have important implications in the prostatic growth (Culig et al, 1996;Ikeda et al, 2000;Rick et al, 2011;Vikram et al, 2010c).…”

“…A recent study by Lee et al, explores the nuclear activities of lipids, showing that dilauroyl phosphotidlycholine controls transcriptional program through nuclear-receptor dependent pathway (Ingraham, 2011;Lee et al, 2011). The study was of particular interest as phosphotidylcholine reversed some of the consequences of high-fat diet feeding (Lee et al, 2011), which is known to promote the cellular proliferation, contractility and overall enlargement of the prostate in rodents (Vikram et al, 2010c). The nuclear signaling and transcriptional regulation by lipids implies that targeting nuclear lipid signaling might be of value in finding the answers for the diseases associated with dietary habit and sedentary lifestyle such as insulin-resistance, type 2 diabetes, several cancers and BPH.…”

“…Previous experimental studies in our laboratory suggested that insulin-resistance associated secondary rise in the plasma insulin level plays a central role in the prostatic enlargement Vikram et al, 2010a;Vikram et al, 2010c;. Other peptides such as insulinlike growth factor-I (IGF-I), IGF-I binding proteins (IGFBPs), growth hormone (GH), transforming growth factor-(TGF-β) family proteins are reported to have important implications in the prostatic growth (Culig et al, 1996;Ikeda et al, 2000;Rick et al, 2011;Vikram et al, 2010c). However, information on the role of lipids in the prostatic growth is scarce and there is a need of further research in this area.…”

“…Augmented steroidal signaling and mesenchymal-epithelial interactions are required for the normal as well as pathological growth of the prostate gland (Marker et al, 2003). However, current literature indicates that apart from steroids, peptides and lipids are also playing a crucial role in the pathogenesis of BPH (Cai et al, 2001;Culig et al, 1996;Escobar et al, 2009;Kaplan-Lefko et al, 2008;Rahman et al, 2007;Rick et al, 2011;Story, 1995;Vikram et al, 2010c). Even if the effects of peptides and lipids on the growth of the gland is milder as compared to that of steroids, chronic change in their levels either due to dietary habit or genetic predispositions can significantly contribute to the initiation and/or progression of the disease over a period of time.…”